烯醇化酶-1在血液系统恶性肿瘤中的作用及机制研究进展

doi:10.3969/j.issn.1003-9198.2026.03.017

摘要/Abstract

摘要： 烯醇化酶-1(ENO1)是糖酵解途径中的关键代谢酶,能催化2-磷酸甘油酸(2-PGA)转化为磷酸烯醇式丙酮酸(PEP),并具有纤溶酶原受体及RNA结合蛋白等多重功能。近年来,大量研究发现ENO1在多种实体瘤及血液系统恶性肿瘤中普遍高表达,提示其在肿瘤发生发展中具有重要的生物学和临床价值。鉴于ENO1在肿瘤代谢重编程和恶性肿瘤进展中的核心作用,深入探讨其功能及机制或可为寻找新的预后标志物和治疗靶点提供依据。本文将重点综述ENO1在急性髓系白血病(AML)、非霍奇金淋巴瘤(NHL)及多发性骨髓瘤(MM)等血液肿瘤中的研究进展、作用途径及分子机制,并介绍特异性烯醇化酶抑制剂(ENOblock)在抗肿瘤治疗中的潜在应用前景。

关键词: 烯醇化酶-1, 烯醇化酶抑制剂, 血液系统肿瘤, 糖酵解

Abstract: Enolase-1 (ENO1) is a key metabolic enzyme in the glycolytic pathway, catalyzing the conversion of 2-phosphoglycerate (2-PGA) to phosphoenolpyruvate (PEP). It also possesses multiple functions, including plasminogen receptor and RNA-binding protein. In recent years, numerous studies have demonstrated that ENO1 is universally overexpressed in various solid tumors and hematologic malignancies, suggesting its biological and clinical significance in tumor development. Given the pivotal role of ENO1 in tumor metabolic reprogramming and malignant tumor progression, further investigation into its functions and mechanisms may provide a basis for identifying novel prognostic markers and therapeutic targets. This article will focus on reviewing the research progress, mechanisms of action, and molecular pathways of ENO1 in hematologic malignancies such as acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM), and introduce the potential application prospects of specific enolase inhibitors (ENOblock) in antitumor therapy.

Key words: enolase-1, inhibitor of enolase, hematological malignancies, glycolysis

中图分类号:

R 733

董佳晖, 徐嘉轩, 周佳乐, 陈兵. 烯醇化酶-1在血液系统恶性肿瘤中的作用及机制研究进展[J]. 实用老年医学, 2026, 40(3): 309-314.

DONG Jiahui, XU Jiaxuan, ZHOU Jiale, CHEN Bing. Search progress on the role and mechanism of enolase-1 in hematological malignancies[J]. Practical Geriatrics, 2026, 40(3): 309-314.

参考文献

[1] VAN DE DONK N, PAWLYN C, YONG K L. Multiple myeloma [J]. Lancet, 2021, 397(10272): 410-427.
[2] DIMOPOULOS M A, JAKUBOWIAK A J, MCCARTHY P L, et al. Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma[J]. Blood Cancer J, 2020, 10(2): 17.
[3] TAKAHARA T, NAKAMURA S, TSUZUKI T, et al. The immunology of DLBCL [J]. Cancers: Basel, 2023, 15(3).
[4] STUBBINS R J, FRANCIS A, KUCHENBAUER F, et al. Management of acute myeloid leukemia: a review for general practitioners in oncology[J]. Curr Oncol, 2022, 29(9): 6245-6259.
[5] HUANG C K, SUN Y, LV L, et al. ENO1 and cancer [J]. Mol Ther Oncolytics, 2022, 24: 288-298.
[6] LI Y, LIU L, LI B. Role of ENO1 and its targeted therapy in tumors[J]. J Transl Med, 2024, 22(1): 1025.
[7] CAPPELLO P, PRINCIPE M, BULFAMANTE S, et al. Alpha-Enolase (ENO1), a potential target in novel immunotherapies[J]. Front Biosci, 2017, 22(5): 944-959.
[8] ZHANG L, LI X, GAO H, et al. Gut microbiota-lncRNA/circRNA crosstalk: implications for different diseases[J]. Crit Rev Microbiol, 2025, 51(3): 499-513.
[9] ALMAGUEL F A, SANCHEZ T W, ORTIZ-HERNANDEZ G L, et al. Alpha-enolase: emerging tumor-associated antigen, cancer biomarker, and oncotherapeutic target[J]. Front Genet, 2021, 11: 614726.
[10] CHUNG I C, HUANG W C, HUANG Y T, et al. Unrevealed roles of extracellular enolase-1 (ENO1) in promoting glycolysis and pro-cancer activities in multiple myeloma via hypoxia-inducible factor 1α[J]. Oncol Rep, 2023, 50(5): 205.
[11] ZHU X, MIAO X, WU Y, et al. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in non-Hodgkin’s lymphomas[J]. Exp Cell Res, 2015, 335(2): 216-223.
[12] LIU J, YANG Q, SUN H, et al. The circ-AMOTL1/ENO1 axis implicated in the tumorigenesis of OLP-associated oral squamous cell carcinoma[J]. Cancer Manag Res, 2020, 12: 7219-7230.
[13] WANG N, QIAO H, HAO J, et al. RNA-binding protein ENO1 promotes the tumor progression of gastric cancer by binding to and regulating gastric cancer-related genes[J]. J Gastrointest Oncol, 2023, 14(2): 585-598.
[14] YANG T, SHU X, ZHANG H W, et al. Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis[J]. Cell Death Dis, 2020, 11(10): 870.
[15] ZHANG L, WANG H, DONG X. Diagnostic value of α-enolase expression and serum α-enolase autoantibody levels in lung cancer[J]. J Bras Pneumol, 2018, 44(1): 18-23.
[16] TU S H, CHANG C C, CHEN C S, et al. Increased expression of enolase alpha in human breast cancer confers tamoxifen resistance in human breast cancer cells[J]. Breast Cancer Res Treat, 2010, 121(3): 539-553.
[17] WANG C, XU R, SONG J, et al. Prognostic value of glycolysis markers in pancreatic cancer: a systematic review and meta-analysis[J]. Front Oncol, 2022, 12: 1004850.
[18] SUN L, SUO C, ZHANG T, et al. ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism[J]. Nat Chem Biol, 2023, 19(12): 1492-1503.
[19] ZHU W, LI H, YU Y, et al. Enolase-1 serves as a biomarker of diagnosis and prognosis in hepatocellular carcinoma patients[J]. Cancer Manag Res, 2018, 10: 5735-5745.
[20] DIMOPOULOS M A, MERLINI G, BRIDOUX F, et al. Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group[J]. Lancet Oncol, 2023, 24(7): e293-e311.
[21] MOHAN LAL B, VAN RHEE F, AL HADIDI S. Current state of evidence on definitions and management of high-risk multiple myeloma[J]. Curr Oncol Rep, 2025, 27(3): 258-277.
[22] HAMAGUCHI T, IIZUKA N, TSUNEDOMI R, et al. Glycolysis module activated by hypoxia-inducible factor 1alpha is related to the aggressive phenotype of hepatocellular carcinoma[J]. Int J Oncol, 2008, 33(4): 725-731.
[23] GAO X, FENG Q, ZHANG Q, et al. Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis[J]. J Biomed Sci, 2025, 32(1): 9.
[24] RAY A, SONG Y, DU T, et al. Preclinical validation of Alpha-enolase (ENO1) as a novel immunometabolic target in multiple myeloma[J]. Oncogene, 2020, 39(13): 2786-2796.
[25] ARMITAGE J O, GASCOYNE R D, LUNNING M A, et al. Non-Hodgkin lymphoma[J]. Lancet, 2017, 390(10091): 298-310.
[26] WEISS J, RENEAU J, WILCOX R A. PTCL, NOS: an update on classification, risk-stratification, and treatment[J]. Front Oncol, 2023, 13: 1101441.
[27] DAI L, FAN G, XIE T, et al. Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis andexhausted immune microenvironment in diffuse large B-cell lymphoma[J]. Biomark Res, 2024, 12(1): 58.
[28] LUDVIGSEN M, BJERREGÅRD PEDERSEN M, LYSTLUND LAURIDSEN K, et al. Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified[J]. Blood Adv, 2018, 2(19): 2533-2542.
[29] SHIMONY S, STAHL M, STONE R M. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management[J]. Am J Hematol, 2023, 98(3): 502-526.
[30] LIU H. Emerging agents and regimens for AML[J]. J Hematol Oncol, 2021, 14(1): 49.
[31] LINCZ L F, THERON D Z, BARRY D L, et al. High expression of ENO1 and Low levels of circulating anti-ENO1 autoantibodies in patients with myelodysplastic neoplasms and acute myeloid leukaemia [J]. Cancers: Basel, 2024, 16(5).
[32] WANG Y, LIU Y, XU Y, et al.AML1-ETO-related fusion circular RNAs contribute to the proliferation of leukemia cells[J]. Int J Mol Sci, 2022, 24(1): 71.
[33] ZHANG W, LIU B, WU S, et al. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia[J]. Open Med, 2023, 18(1): 20220602.
[34] NOVIKOVA S, TOLSTOVA T, KURBATOV L, et al. Nuclear proteomics of induced leukemia cell differentiation [J]. Cells, 2022, 11(20).
[35] WANG J, WANG H, DING Y, et al. NET-related gene signature for predicting AML prognosis [J]. Sci Rep, 2024, 14(1): 9115.
[36] XU B, ZHOU Z, WEN Y, et al. The immunometabolic landscape of the bone marrow microenvironment in acute myeloid leukemia [J]. Exp Hematol Oncol, 2022, 11(1): 81.
[37] JUNG D W, KIM W H, PARK S H, et al. A unique small molecule inhibitor of enolase clarifies its role in fundamental biological processes [J]. ACS Chem Biol, 2013, 8(6): 1271-1282.
[38] SATANI N, LIN Y H, HAMMOUDI N, et al. ENOblock does not inhibit the activity of the glycolytic enzyme enolase [J]. PLoS One, 2016, 11(12): e0168739.
[39] CHO H, UM J, LEE J H, et al. ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes [J]. Sci Rep, 2017, 7: 44186.